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drug adverse effects of SSRIs

Adverse effects: 1) serotonin syndrome 2) withdrawal reactions after discontinuation [8,15,21,25] a) more common with short-acting SSRIs, especially paroxetine b) dizziness, gait instability c) electric shock sensations d) headache e) nausea [25] f) delirium [21] f) generally occur 1-3 days after discontinuation g) generally resolve within 10 days 2) GI bleeding* (< 2%) - mitigated by concurrent administration of proton pump inhibitor [19] 3) SIADH & hyponatremia [4] 4) may inhibit growth hormone secretion & thus growth in children [5] 5) in utero effects [7,11,13] a) lower Apgar scores at birth b) delayed fine motor development c) SSRI-induced neonatal withdrawal syndrome (30%) [13,14] d) newborn pulmonary hypertension associated with SSRI use in 2nd & 2rd trimester, perhaps related to serotonin- mediated pulmonary vasoconstriction (HR=2.1) [13,14,24] e) increased, but rare congenital anomalies associated with SSRI use in 1st trimester [22] 1] cardiovascular anomalies (fluoxetine, paroxetine) - septal defects & right ventricular outflow tract defects [33] 2] neural tube defects citalopram 3) fetal alcohol spectrum disorders f) no substantial increase in prevalence of overall cardiac birth defects [33] g) increased risk of autism in offspring of pregnant women using SSRI [23] - relative risk < 1.61 [29]; 2.17 [36] h) not associated with stillbirth or infant mortality [27] i) weight at 1 year not affected by SSRI use or depression during pregnancy [28] j) exposure to SSRI in late pregnancy (>= 20 weeks of gestation) increases risk of pulmonary hypertension in newborns (RR = 2.5) [30] k) SSRI exposure reduces risks for preterm birth & C section in mothers with psychiatric diagnoses [35] l) increased likelihood of newborn admission to the NICU [37] m) discontinuation of SSRI during pregnancy associated with depression relapse, prematurity, & postpartum depression that may negatively affect a child's development [37] 6) may be associated with bone loss [16] - may increase risk of fracture in perimenopausal women [34] 7) exacerbation of parkinsonism [17] 8) SSRIs worsen symptoms of restless legs syndrome [25] 9) REM sleep behavioral disorder [25] 10) may trigger manic attack in bipolar affective disorder, especially when not combined with lithium carbonate 11) increase in stroke risk in post-menopausal women, largely due to an increase in hemorrhagic stroke (consistent with SSRI's antiplatelet effects) (hazzard ratio 1.45) - increased risk of intracranial hemorrhage in the general population [26] (1 additional case of hemorrhagic stroke per 10,000 patients/year) 12) increased risk of mortality when SSRI initiated after stroke [32] 13) sexual dysfunction, orgasm disorders [21] - commonly associated with decreased libido & erectile dysfunction [21] - substitute with or add bupropion [40] 14) higher SSRI doses may be associated with self-harm in children & young adults [31] - no association is adults > 60 years of age [26] 15) increased risk for violence & aggressive behavior? [38] 16) increased risk of falls in the elderly 36-39% in first year [39] 17) QTc prolongation (see drug-induced prolongation of the QT interval) * diminished serotonin in platelets due to diminished uptake [2,3,6,9,18] * patients with anxiety disorder should be counseled on potential of adverse effects & when they do occur are likely to be benign & shortlived, often a manifestation of the underlying disorder [25] Complications: - suicide children, adolescents [10], adults [11] - no association is adults > 60 years of age [26]

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DRUGS: serotonin reuptake inhibitor FORM: drug adverse effects serotonin reuptake inhibitor

References

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